Using rat ventral prostate as a model androgen-sensitive tissue, it is proposed to characterize fully a method for the assay of nuclear androgen receptor concentration after exchange incubation in a nucler KCl extract. The salt-resistant nuclear binding capacity will also be assayed after incubation of tissue minces. Results from these in vitro experiments will be compared with nuclear androgen binding capacity in animals injected with labelled 3H-dihydrotestosterone, to establish that the in vitro events truly reflect physiological events occurring in vivo. It is proposed to examine whether the reported secondary androgen-independent rise of cytosol AR concentration in castrated rats is accompained by a rise in concentration of nuclear androgen binding cpacity in these animals. The in vitro methods will be applied to human prostatic tissue to extend our preliminary observations, which suggest that nuclear AR concentration is determined by the concentration of occupied cytosol AR. The results obtained will be integrated with data on cytosol AR in the same tissue, the histopathology of the tissue, the endocrine status of the patients and wherever possible, to their response to hormonal manipulative treatment. The hypothesis that some prostatic carcinomas contain non-functional cytosol AR which is not retained in the nucleus will be examined by the incubation of tissue with labelled ligand. Data on the human tissue will be examined in relation to clinical response to see if it is possible to identify a 'threshold' concentration of nuclear binding, below which androgen sensitivity is lost.